Combined cytotoxic effect of UV-irradiation and TiO2 microbeads in normal urothelial cells, low-grade and high-grade urothelial cancer cells

Abstract

The differentiation of urothelial cells results in normal terminally differentiated cells or by alternative pathways in low-grade or high-grade urothelial carcinomas. Treatments with traditional surgical and chemotherapeutical approaches are still inadequate and expensive, as bladder tumours are generally highly recurrent. In such situations, alternative approaches, using irradiation of the cells and nanoparticles, are promising. The ways in which urothelial cells, at different differentiation levels, respond to UV-irradiation (photolytic treatment) or to the combination of UV-irradiation and nanoparticles (photocatalytic treatment), are unknown. Here we tested cytotoxicity of UV-irradiation on (i) normal porcine urothelial cells (NPU), (ii) human low-grade urothelial cancer cells (RT4), and (iii) human high-grade urothelial cancer cells (T24). The results have shown that 1 minute of UV-irradiation is enough to kill 90% of the cells in NPU and RT4 cultures, as determined by the live/dead viability assay. On the other hand, the majority of T24 cells survived 1 minute of UV-irradiation. Moreover, even a prolonged UV-irradiation for 30 minutes killed <50% of T24 cells. When T24 cells were pre-supplemented with mesoporous TiO2 microbeads and then UV-irradiated, the viability of these high-grade urothelial cancer cells was reduced to <10%, which points to the highly efficient cytotoxic effects of TiO2 photocatalysis. Using electron microscopy, we confirmed that the mesoporous TiO2 microbeads were internalized into T24 cells, and that the cell's ultrastructure was heavily compromised after UV-irradiation. In conclusion, our results show major differences in the sensitivity to UV-irradiation among the urothelial cells with respect to cell differentiation. To achieve an increased cytotoxicity of urothelial cancer cells, the photocatalytic approach is recommended.

Multifunctional Gadolinium‐Doped Mesoporous TiO2 Nanobeads: Photoluminescence, Enhanced Spin Relaxation, and Reactive Oxygen Species Photogeneration, Beneficial for Cancer Diagnosis and Treatment

“…Based on this critical feature, recently we have engineered mesoporous TiO 2 nanobeads (TiO 2 NBs) having a size greater than 100 nm, to avoid normal nanotoxicity, and on the other hand keeps the high surface area comparable to nanometer‐size particles by utilizing mesoporosity. TiO 2 NBs totally were biocompatible in the absence of irradiation that also possesses a high ability for ROS photogeneration and cancer cell destruction under UV‐A irradiation . Here we report doping of TiO 2 NBs with the rare earth element Gd to add multifunctional OI–MRI properties, as well enhanced ROS photogeneration capacity to the TiO 2 NBs.…”

“…TiO 2 NBs totally were biocompatible in the absence of irradiation that also (3 of 11) 1700349 www.small-journal.com possesses a high ability for ROS photogeneration and cancer cell destruction under UVA irradiation. [5,32] Here we report doping of TiO 2 NBs with the rare earth element Gd to add multifunctional OI-MRI properties, as well enhanced ROS photogeneration capacity to the TiO 2 NBs. The photocatalytic activities of the TiO 2 @xGd NBs in terms of ROS photogeneration were quantified via • OH radical measurement with fluorescence probe and com pared with a standard TiO 2 powder (P25). The details of the bandgap states introduced by the Gddoping, and the conse quences for the photoluminescence (PL) and photo catalytic enhancement are investigated and supported by density functional theory (DFT) calculations.…”

Modulation of voltage-gated conductances of retinal horizontal cells by UV-excited TiO2 nanoparticles

“…Nevertheless, it has been shown that prolonged (24 hours) exposure to TiO nanoparticles can effect mitochondrial function (35), and two-year exposure to high concentrations of TiO 2 nanoparticles has been found to cause pulmonary lesions in rats (36). UVphotoactivated TiO 2 nanoparticles have also been shown to generate reactive oxygen species (ROS) which could make cells more susceptible to bacterial invasion (37) and cause other cell damage after several hours of exposure (38)(39)(40). While no adverse effects were observed on the time scale of the experiment, more research is needed before implementing photoactive TiO 2 in long-term studies or therapeutics.…”

The role of membrane vesiculation and encapsulation in cancer diagnosis and therapy

“…Considering that the electrode system is not the most appropriate configuration for such application, water-soluble particulated TiO 2 e which could cover a larger effective surface area and can be incorporated inside cells e was applied for this purpose [129]. Under different experimental conditions using UV-A irradiation, various research groups demonstrated in vitro the phototoxic effect of TiO 2 nanoparticles (NPs) on a series of human cancer cells such as cervical cancer cells (HeLas) [130], bladder cancer cells (T24) [131], monocytic leukemia cells (U937) [132], adenocarcinoma cells (SPC-A1) [133], colon carcinoma cells (Ls-174-t) [134], breast epithelial cancer cells (MCF-7, MDA-MB-468) [135], glioma cells (U87) [136] and human hepatoma cells (Bel 7402) [137]. In the past decade, much research was dedicated to the photocatalytic destruction of cancerous cells with TiO 2 nanomaterials in vitro as well as in vivo, yet the practical use of TiO 2 as a photosensitizer in PDT for cancer destruction is still far from being put into practice [128,138,139].…”